CDCP1 explained

CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1 gene.^{[1] [2]} CDCP1 has also been designated as CD318 (cluster of differentiation 318) and Trask (Transmembrane and associated with src kinases). Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Function

CDCP1 is a 140 kD transmembrane glycoprotein with a large extracellular domain (ECD) containing two CUB domains, and a smaller intracellular domain (ICD). CDCP1 is cleaved by serine proteases at the extracellular domain next to Arg368 to generate a truncated molecule of 80 kDa size.^[3] Different cell lines express different amounts of p140 and p80, depending on the activity of endogenous serine proteases.

The intracellular domain of CDCP1 contains five tyrosine residues - Y707, Y734, Y743, Y762 and Y806. The tyrosine phosphorylation of CDCP1 in cultured cells occurs when cells are induced to detach by trypsin or EDTA, or seen spontaneously during mitotic detachment.

Clinical significance

The phosphorylation of CDCP1 is seen in many cancers, including some pre-invasive cancers as well as in invasive tumors and in tumor metastases.^[4]

Further reading

• Xia Y, Gil SG, Carter WG . Anchorage mediated by integrin alpha6beta4 to laminin 5 (epiligrin) regulates tyrosine phosphorylation of a membrane-associated 80-kD protein . The Journal of Cell Biology . 132 . 4 . 727–40 . February 1996 . 8647901 . 2199869 . 10.1083/jcb.132.4.727 .
• Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE, Quigley JP . Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen . Oncogene . 22 . 12 . 1783–94 . March 2003 . 12660814 . 10.1038/sj.onc.1206220 . 2608191 .
• Conze T, Lammers R, Kuci S, Scherl-Mostageer M, Schweifer N, Kanz L, Buhring HJ . CDCP1 is a novel marker for hematopoietic stem cells . Annals of the New York Academy of Sciences . 996 . 1 . 222–6 . May 2003 . 12799299 . 10.1111/j.1749-6632.2003.tb03249.x . 2003NYASA.996..222C . 12794175 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Brown TA, Yang TM, Zaitsevskaia T, Xia Y, Dunn CA, Sigle RO, Knudsen B, Carter WG . Adhesion or plasmin regulates tyrosine phosphorylation of a novel membrane glycoprotein p80/gp140/CUB domain-containing protein 1 in epithelia . The Journal of Biological Chemistry . 279 . 15 . 14772–83 . April 2004 . 14739293 . 10.1074/jbc.M309678200 . free .
• Bühring HJ, Kuçi S, Conze T, Rathke G, Bartolović K, Grünebach F, Scherl-Mostageer M, Brümmendorf TH, Schweifer N, Lammers R . CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin . Stem Cells . 22 . 3 . 334–43 . 2005 . 15153610 . 10.1634/stemcells.22-3-334 . 11997172 .
• Benes CH, Wu N, Elia AE, Dharia T, Cantley LC, Soltoff SP . The C2 domain of PKCdelta is a phosphotyrosine binding domain . Cell . 121 . 2 . 271–80 . April 2005 . 15851033 . 10.1016/j.cell.2005.02.019 . 1498824 . free .
• Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM . Adhesion signaling by a novel mitotic substrate of src kinases . Oncogene . 24 . 34 . 5333–43 . August 2005 . 16007225 . 3023961 . 10.1038/sj.onc.1208582 .
• André M, Le Caer JP, Greco C, Planchon S, El Nemer W, Boucheix C, Rubinstein E, Chamot-Rooke J, Le Naour F . Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS . Proteomics . 6 . 5 . 1437–49 . March 2006 . 16404722 . 10.1002/pmic.200500180 . 46542257 .
• Kimura H, Morii E, Ikeda JI, Ezoe S, Xu JX, Nakamichi N, Tomita Y, Shibayama H, Kanakura Y, Aozasa K . Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells . Leukemia . 20 . 9 . 1551–6 . September 2006 . 16926850 . 10.1038/sj.leu.2404312 . 6809573 .
• Perry SE, Robinson P, Melcher A, Quirke P, Bühring HJ, Cook GP, Blair GE . Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells . FEBS Letters . 581 . 6 . 1137–42 . March 2007 . 17335815 . 10.1016/j.febslet.2007.02.025 . 30701692 .
• Uekita T, Jia L, Narisawa-Saito M, Yokota J, Kiyono T, Sakai R . CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma . Molecular and Cellular Biology . 27 . 21 . 7649–60 . November 2007 . 17785447 . 2169043 . 10.1128/MCB.01246-07 .

Notes and References

1. Scherl-Mostageer M, Sommergruber W, Abseher R, Hauptmann R, Ambros P, Schweifer N . Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer . Oncogene . 20 . 32 . 4402–8 . July 2001 . 11466621 . 10.1038/sj.onc.1204566 . 19987585 .
2. Web site: Entrez Gene: CDCP1 CUB domain containing protein 1.
3. Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM . Adhesion signaling by a novel mitotic substrate of src kinases . Oncogene . 24. 34 . 5333–43. 2005 . 16007225 . 3023961 . 10.1038/sj.onc.1208582.
4. Wortmann A, He Y, Deryugina EI, Quigley JP, Hooper JD . The cell surface glycoprotein CDCP1 in cancer--insights, opportunities, and challenges . IUBMB Life . 61 . 7 . 723–30 . July 2009 . 19514048 . 10.1002/iub.198 . 9630579 . free .